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RESEARCH PRODUCT
Mammalian BiP controls posttranslational ER translocation of the hepatitis B virus large envelope protein.
Reinhild PrangeCarsten LambertKarin Awesubject
Hepatitis B virusgenetic structuresBiPBiophysicsHemagglutinin (influenza)Chromosomal translocationmacromolecular substancesmedicine.disease_causeEndoplasmic ReticulumBiochemistryCell LineAdenosine TriphosphateViral Envelope ProteinsStructural BiologyIn vivoCalnexinHBVGeneticsmedicineHumansMolecular BiologyEndoplasmic Reticulum Chaperone BiPTranslocational regulationHeat-Shock ProteinsHepatitis B virusbiologyEndoplasmic reticulumMembrane ProteinsCell BiologyHSP40 Heat-Shock ProteinsMolecular biologyProtein Structure TertiaryProtein TransportDual topologyMembrane topologyProtein BiosynthesisMembrane topologybiology.proteinPosttranslational translocationMolecular Chaperonesdescription
AbstractThe hepatitis B virus L protein forms a dual topology in the endoplasmic reticulum (ER) via a process involving cotranslational membrane integration and subsequent posttranslational translocation of its preS subdomain. Here, we show that preS posttranslocation depends on the action of the ER chaperone BiP. To modulate the in vivo BiP activity, we designed an approach based on overexpressing its positive and negative regulators, ER-localized DnaJ-domain containing protein 4 (ERdj4) and BiP-associated protein (BAP), respectively. The feasibility of this approach was confirmed by demonstrating that BAP, but not ERdj4, destabilizes the L/BiP complex. Overexpressing BAP or ERdj4 inhibits preS posttranslocation as does the reduction of ATP levels. These results hint to a new role of BiP in guiding posttranslational polypeptide import into the mammalian ER.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-08-15 | FEBS letters |